Genetic counseling: Polycystic Kidney Disease
Polycystic Kidney Disease Introduction *Greet the family/parent *What do you understand about why you are here in genetics today? *What questions or concerns do you want to have addressed today? Elicit Medical History (interim history form) *update medical history since last seen *determine if there have been any problems since released from the hospital *assess developmental history Update Family History *Update pedigree *determine if there are any other family members with kidney problems, heart problems, liver problems or that died in early infancy What is Polycystic Kidney Disease (PKD)? *Two main types **Autosomal Dominant PKD (adult PKD) **Autosomal Recessive PKD (infantile PKD) ADPKD *Etiology and Natural History **gene PKD1 mutated in about 85% of cases **gene PKD2 mutated in about 15% of cases symptoms usually develop beginning in early adulthood although can be found in the infant period or not begin until later in adulthood **large amount of variability both within and between families *Prevelance and Inheritance **most common single gene disorder that is potentially lethal **prevalence at birth: 1/400 - 1/1000 **10% of cases due to new mutation **occurs in all races **inherited in autosomal dominant fashion ***if one parent is affected there is a 50% chance of having an affected child *Symptoms **multiple bilateral renal cysts (100% of cases) ***leads to end stage renal insufficiency by 60 years old in 50% of cases **cysts in other organs specifically the liver (20% by 3rd decade; 75% by 6th decade) **intracranial aneurysms (10% of cases) ***more common in patients with family history of intracranial aneurysms (22%) than those without this history (6%) **mitral valve prolapse and other heart defects *Diagnosis **patients with known 50% risk ***at least 2 cysts either unilateral or bilateral by 30years of age ***large kidneys without cysts in infants and children **patients with no known risk ***bilateral renal enlargements and cysts ***in absence of indication for different renal cystic disease ***suggestive of ADPKD, but not definite diagnosis **Differential from: ***ARPKD - unaffected parents ***Glomerulocystic kidney disease - minimal tubular involvement *Molecular Testing **Linkage analysis - need a large number of family members to establish which gene is responsible **Prenatal Testing - only available after a mutation has been identified in an affected family member *Management **no treatment for disease itself **treat symptoms to prevent premature death and alleviate pain ARPKD *Etiology and Natural History **mutation in PKHD1 locus (6p21) present in all studied patients with ARPKD **enlarged echogenic kidneys found in perinatal period **large amount of variability both within and between families **30% of patients with ARPKD die in neonatal period *Prevelance and Inheritance **prevalence: 1/20,000 - 1/40,000 **prevelance may be underestimated due to death in neonatal period **carrier frequency: 1/70 **inherited in autosomal recessive fashion ***if both parents are carriers there is a 25% chance of having a child who is affected , 50% chance of having a child who is a carrier, and a 25% chance of having *Symptoms **enlarged, echogenic kidneys with poor differentiation (100% of cases) ***renal function impaired in 70-80% of cases **hypertension ***usually occurs within first week of life **Liver disease (45% of cases at presentation) **pulmonary hypoplasia resulting from oligohydramnios **other abnormalities: low set ears, micrognathia, flattended nose, growth deficiency *Diagnosis **enlarged echogenic kidneys with poor differentiation **one or more of the following: ***absence of renal cysts in parents ***signs of hepatic fibrosis ***pathoanatomical proof of ARPKD in affected sibling ***parental consanguinity suggesting AR inheritance **Differential from: ***ADPKD - more likely to have bilateral macrocysts ***Glomerulocystic kidney disease - minimal tubular involvement *Molecular Testing **Linkage analysis - based on accurate diagnosis of ARPKD in affected individual and accurate understanding of relationships in family **Prenatal Testing - only available after a linkage has been identified in an affected family member *Management **no treatment for disease itself **treat symptoms to prevent premature death and alleviate pain ***stabilize respiratory function **feeding difficulty and growth failure in chidren Psychosocial Issues *uncertainty of diagnosis and prognosis may lead to anxiety *possibity that parent could find out they have the diease (for ADPKD) *guilt over passing trait to child *Concern for risks to future pregnancies *Are you interested in pursuing linkage analysis? *How are you dealing with your son's health problems? *Are you anxious about the possibility of upcoming surgeries? *Reassure that this could not have been prevented Recommended Follow-up for PKD *renal ultrasounds to monitor cysts and function *control of hypertension *CT scan to detect aneurysm (ADPKD) *monitor liver function Resources *PKD foundation (www.pkdcure.com) References *Practical Genetic Counseling *OMIM *GeneClinics *GeneTests *Human Congenital Malformations Notes The information in this outline was last updated in 2002. This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.